A conclusion one could draw from the first two chapters is that the role of genes in determining phenotypes is complex and dynamic. That is true. It is an important insight that should be kept in mind when evaluating a genetic question. But, by the same token, complexity does not necessarily mean that rules and order are weak. In this chapter we will explore some of these rules, specifically the question of how gene regulation activates a particular gene in the appropriate developmental context and how molecular signals carry out large-scale patterning to organize the structure of the body in early development.
To a degree that still impresses most biologists, there is extensive similarity, or homology, in the genes that control development in humans and in model organisms like fruit flies, nematodes, and zebrafish. These homologies underlie the unity of life. The insights the field has gained from model organisms will help tell the story of genetic control of development in humans.
Part 1: Background and Systems Integration
Overview of Timing and the Processes at Work
The nuclear control of development does not actually begin when the genes of an egg and a sperm fuse at fertilization. The earliest stages of embryonic development are actually controlled by the mother's genome. Molecular signals like inducers and mRNA coded by the maternal genome are stored in the cytoplasm during egg formation. Very few genes in the new individual are transcribed at first. Genetic influences at this early stage are called maternal effects. Details vary among organisms, but basically the fertilized egg nucleus divides several times to become a ball of cells, the morula. The cells then form a fluid-filled ball, the blastula or in mammals the blastocyst, in which cells are set off to one side. The internal space keeps cells that will become ectoderm and endoderm from interacting prematurely and provides a space for cell movement. In humans the embryo forms the morula as it travels along the fallopian tube, and by 41/2 to 5 days it has formed into a blastocyst and enters the uterine cavity. This blastocyst implants into the uterine wall about 6 days after fertilization.
It is at this blastula stage that the embryo's own genes first become active and take over control of development. One process that may trigger this transition is the demethylation of various promoters that then bind with transcription factors to initiate transcription. At that point there can be cytoplasmic differences among the blastula cells, blastomeres, due to process like the partitioning of inducers and RNA molecules in the original egg cytoplasm. The resulting transcriptional cascades in different parts of the blastula ultimately contribute to the patterned organization of tissues, organs, and organ systems of the fetus and adult.
The process of early development can be conveniently described in terms ...